cartouche ECN WORKSHOP



C. Sungkweon 1, C. A. Winkler 2, B. Stiburkova 3,4

1. Department of Health Sciences and Technology, Saihst, Sungkyunkwan University, Seoul, Republic of Korea 2. Molecular Genetic Epidemiology Section, Basic Research Laboratory, Frederick National Laboratory for cancer research, National Cancer Institute, Frederick, MD, USA; 3. Institute of Rheumatology, Prague, Czech Republic; 4. Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic


Objective: Xanthinuria is a rare inherited disorder of purine metabolism (1 in 69,000). In the first step, determination of serum and urinary uric acid and purine profile isimportant to establish the diagnosis of xanthinuria. Second, xanthinuria is typed using urinary metabolomics. Finally, the results are confirmed by molecular genetics.1 Here, we aimed to identify genetic variants in the xanthiuria patient using whole-exome sequencing (WES) and evaluated its functional variants.

Methods: 43-year-old female (Roma ethnic group) visited the outpatient clinic. She was diagnosed as xanthinuria based on biochemical lab data (serum uric acid 70 µmol/L, FE-UA: 8.6%, urinary hypoxanthine 52.6 mmol/molCr and urinary xanthine 186.3 mmol/molCr). Conventional genotyping of XDH/XO, AOX and MOCOS does not find the causal variant. WES and corresponding downstream analyses were performed for the discovery of coding causal variants further evaluation and we compared the result to WES of 31 hypouricemia patients in Korean.

Results: Considering its prevalence and recessive inheritance, 34 candidate variants were identified after filtering out allele frequency threshold in Non-Finish European. Based on known gene list, homozygote mutation of p.Leu19Phe in MOCS2 (MIM : 603708) was identified for the causal variants. Functional prediction tool indicated that the variants was found to be damaging (0.58, Polyphen2), disease causing (0.686, Mutation Taster) and CADD score of 16.62. After investigating 31 hypouricemic Korean patients for the replication, we found a truncating p.Arg132* variant of MOCS1 (MIM: 603707) in patients who have homozygous variants of SLC22A12.

Conclusion: This shows the value of MOCS genes for xanthinuria for the first time.